Biomedical subjects

K Inada

Publications and source records attributed to K Inada.

At least 127 records · Page 7Linked to original sources

PubMed1994

Blood cytokine and complement levels in patients with sepsis.

We measured serum levels of endotoxin, cytokines, and eicosanoids and investigated their relationship to serum complement levels in patients with sepsis. Serum endotoxin (Et) levels (5.3 +/- 2.4 pg/ml) were within the normal range, but levels of tumor necrosis factor-alpha (TNF-alpha, 114 +/- 104.94 pg/ml), interleukin 6 (IL-6, 86.7 +/- 50.9 pg/ml), interleukin 8 (IL-8, 86.8 +/- 49.7 pg/ml), type-II phospholipase A2 (type II PLA2, 211.3 +/- 193.9 ng/ml), leukotriene B4 (LTB4, 88.7 +/- 27.2 pg/ml), thromboxane B2 (TXB2, 58.7 +/- 50.9 pg/ml) and 6-keto-prostaglandin F1 alpha (PGF1 alpha, 21.0 +/- 11.0 pg/ml) levels were above normal. Levels of C3a (1088.4 +/- 83.8.7 ng/ml) and C4a (1951.5 +/- 1697.8 ng/ml) were also above normal; C3 (66.0 +/- 25.6 mg/dl) and C4 (23.6 +/- 5.3 mg/dl) were within the normal range, and C5a was lower than the detectable limit in all but one of the subjects. Serum TNF-alpha was significantly correlated with C3a (p < 0.001). Serum IL-6 had a significant negative correlation with C3 (p = 0.002) and C4 (p = 0.010). Type II PLA2 was significantly correlated with C3a (p < 0.001). There were no significant correlations between serum Et or IL-8 and serum C3, C4, C3a or C4a. Our findings suggest that increased levels of TNF-alpha, IL-6, and Type II PLA/ in patients with sepsis contribute to activation of the complement system.

Adult↗

PubMed1994

Polyclonal B cell activation, endotoxin tolerance, and limulus tests of endotoxin preparations of some periodontopathogens.

Potencies of polyclonal B-cell activation in C3H/HeN mice of Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum, and Porphyromonas gingivalis endotoxins were 0.36, 0.13 and 0.04, taking Salmonella abortusequi as 1.0. F. nucleatum and P. gingivalis endotoxins showed positive reactions in C3H/HeJ mice. Most activities in C3H/HeN other than that of F. nucleatum were suppressed by polymyxin B. In C3H/HeJ mice, similar inhibitions were only 60% for P. gingivalis and hardly observed with F. nucleatum. The resistances to polymyxin B could be due to protein in the endotoxins. A promoting effect of T cells added to B cells was observed only in the activity of F. nucleatum endotoxin in C3H/HeJ mice; there was no influence in other groups. Test endotoxins had nearly the same ability to produce colony stimulating factor as did references and could not produce the factor in tolerant mice. The clinical significance of tolerance is discussed. Regression lines of endotoxin doses and limulus activities of test endotoxins and Salmonella were parallel, either in specific or non-specific tests. The lines of two test groups were also parallel; values obtained by two tests were very close. These data indicate that the test endotoxins did not contain (1-3)-beta-D-glucan and elicited qualitatively similar limulus reactions to that of the reference, despite their different chemical natures. In conclusion, these test preparations had an endotoxicity similar to that of the reference and contribute to produce periodontitis through polyclonal B cell activation.

Aggregatibacter actinomycetemcomitans↗

PubMed1994

Platelet-activating factor (PAF) acetylhydrolase activity, type II phospholipase A2, and cytokine levels in patients with sepsis.

Platelet activating factor acetylhydrolase (PAF-AH) activity was measured in patients with sepsis, and its relationships with various cytokines and endotoxin were evaluated. PAF-AH activity was significantly higher (p = 0.0136) in 17 patients who died than 13 patients who survived. PAF-AH activity showed significant correlations with the plasma endotoxin, TNF-alpha, and IL-8 levels. These findings suggest that PAF-AH activity reflects the severity of the pathological condition.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗

PubMed1994

Relationship between thromboxane B2 and 6-keto-prostaglandin F1 alpha in sepsis.

To examine the roles of thromboxane A2 and prostaglandin I2, which are arachidonic acid metabolites found in patients with sepsis, we measured the serum levels of their respective stable metabolites, thromboxane B2 (TXB2) and 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) in 22 patients with sepsis. Results were analyzed in relation to patients' survival. The levels of both TXB2 and 6-keto-PGF1 alpha were significantly higher in patients who died than in those who survived, thus reflecting the severity of the patients' illness. There was a significant correlation between the levels of TXB2 and 6-keto-PGF1 alpha. These findings suggest that TXA2 and PGI2 are chemical mediators involved in the severity of clinical sepsis.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Serum complement levels and severity of sepsis.

The activities (C3a, C4a, C5a) and concentrations (CH50, C3, C4, C5) of serum complement were measured to evaluate the involvement of complement in sepsis. We studied 27 patients with sepsis who were divided into the survivors (Group 1) and the nonsurvivors (Group 2). The levels of C3a, C4a, and C5a were all significantly higher in Group 2 than in Group 1 and closely reflected the severity of sepsis. Levels of C3 and C4 were significantly lower in Group 2 than in Group 1, presumably because these components were consumed as a result of activation of both the alternative and classical pathways. The levels of CH50 and C5 did not differ significantly between the two groups. These findings suggest that complement is closely involved in the exacerbation of the condition of septic patients, and that the measurement of complement activity is useful for evaluating the severity of sepsis.

Adult↗

PubMed1994

Significance of alpha-tocopherol and interleukin 8 in septic adult respiratory distress syndrome.

To elucidate the relationship between active oxygen and interleukin 8 (IL-8) in patients with septic adult respiratory distress syndrome (ARDS), we determined the serum levels of alpha-tocopherol, which has an antioxidant action, and IL-8 in seven patients with this disease. Serum alpha-tocopherol and IL-8 levels determined at the time of diagnosis of septic ARDS were 0.97 +/- 0.36 mg/dl and 0.98 +/- 0.99 ng/ml, respectively. A significant correlation was found between serum alpha-tocopherol level and IL-8 level (r = -0.758, p = 0.0473). These findings suggest that IL-8 activates neutrophils, which produce active oxygen.

Adolescent↗

PubMed1994

[A case of primitive neuroectodermal tumor in the chest wall ("Askin's tumor")].

We report a case of Askin's tumor, primitive neuroectodermal tumor (PNET) in the chest wall, with review of reported cases of PNET. Our case was the ninth of Askin's tumor and the 36th of PNET in Japan. A 12-year-old girl was hospitalized because of a large right intrathoracic mass. The serum neuron-specific enolase (NSE) was 11.4 ng/ml, slightly increased, and the urinary excretion of catecholamine metabolites was normal. The needle biopsy specimens were diagnosed as small round cell sarcoma. At surgery we found an encapsulated multilobular mass in the region. The chest wall was resected partially to extirpate it completely. Its macroscopic and microscopic features were almost similar to the description of Askin et al. The immunohistochemical staining of the cells was positive for NSE, strongly suggesting the neurogenic origin. After surgery, intensive chemotherapy with autologous bone marrow transplant was performed, and she has been living without sign of recurrence for two years.

Child↗

PubMed1994

[Significance of overexpression of p53 protein in human breast cancer].

Overexpression of p53 protein was examined by immunohistochemical assay. In 143 primary breast cancer patients, consisting of 18 patients with family history of breast cancer or past history of breast cancer and 125 patients with no such histories. In the later 125 patients, overexpression of p53 was shown in 42 patients (33.6%), however in the former 18 patients, p53 overexpression was found in 15 (83.3%). It was suggested that p53 protein is frequently overexpressed in patients with high risks like history of breast cancer and family history of breast. On the other hand, regarding the value of p53 overexpression as a prognostic indicator, an univariate analysis demonstrated that the relapse free survival of patients with over 50% p53 positive all rate was significantly worse compared to that of patients with less than 50% p53 positive all rate (p < 0.05). However multivariate analysis did not demonstrate the significant value (p < 0.1), suggesting that overexpression of p53 is marginal as a prognostic indicator.

Breast Neoplasms↗

PubMed1994

Relationship between cytokines and leukotriene B4 in sepsis.

To clarify the relationship between cytokines and arachidonic acid metabolites, we measured tumor necrosis factor (TNF-alpha), interleukin 8 (IL-8), and leukotriene B4 (LTB4). The subjects consisted of 30 patients with sepsis. The results were compared between patients who died (Group A) and those who survived (Group B). All TNF-alpha, IL-8, and LTB4 levels were significantly higher in Group A than in Group B, reflecting the severity of the disease. The LTB4 levels were significantly correlated with the TNF-alpha level and the IL-8 level. These results suggest that inflammatory cytokines, excessively produced due to inflammatory reactions, stimulate as a mediator the release of arachidonic acid, increasing LTB4 production.

Adult↗

PubMed1994

Clinical effects of intramuscular administration of a small dose of polymyxin B to patients with endotoxemia.

The effects of intramuscular injections of minute amounts of polymyxin B were studied in 42 patients with endotoxemia. Plasma endotoxin was measured by means of an endotoxin-specific Endospecy test (Seikagaku Corp., Tokyo, Japan) after pretreatment of the plasma with a new perchloric acid method that we developed. The normal value of plasma endotoxin is less than 9.8 pg/mL. Polymyxin B was administered at a dose of 12,500 U every 6 hours. Plasma endotoxin rapidly decreased to the normal range in 40 of the 42 patients. Body temperature fell significantly. APACHE II scores were also significantly improved. Tumor necrosis factor-alpha and interleukin-6 (IL-6) decreased in survivors, while tending to persist in high values in patients who died. No side effects were observed in any of the patients. In conclusion, intramuscular injections of small doses of polymyxin B were useful in the treatment of endotoxemia.

Adolescent↗

PubMed1993

Characterization of CD4+ single positive cells that lack CD3 in the human thymus.

In the thymus of experimental animals, single positive cells that lack surface CD3 expression (CD3-CD4+CD8- or CD3-CD4-CD8+) have been reported to have intermediate characteristics between the CD4-CD8- cells and CD4+CD8+ cells. Here we show the presence of single positive cells in the human thymus that lack CD3 by means of three-color flow cytometric analysis. CD3- cells constitute 12 +/- 7.5% of CD4 single positive cells in 10 normal thymus samples. CD8 single positive cells, on the other hand, contained only 1.5 +/- 2.2% CD3- cells. Seventeen percent of these CD3-4+8- thymocytes were in S+G2/M phase, while only 4.3% of CD4+CD8- thymocytes were in S+G2/M. The surface antigen phenotype of CD3-CD4+CD8- thymocytes was CD1(low), CD2+, alpha beta TCR-, CD29(high), LFA-1+, ICAM-1-, IL-2R-, CD45common (low), CD45RA-, and CD45R0(low). They expressed cytoplasmic CD3+ and 28% of them expressed cytoplasmic CD3 and cytoplasmic alpha beta TCR. The levels of CD2, CD29, CD45R0, cytoplasmic CD3, and cytoplasmic alpha beta TCR expression were intermediate between the CD3-4-8- and CD4+8+ populations. These results indicate that CD3-CD4+CD8- thymocytes constitute a minor but significant population in the human thymus. Their surface antigen phenotype and the high incidence of dividing cells suggest that they are immature and probably on their way to the CD4+8+ double positive thymocytes.

Adolescent↗

PubMed1993

Increased expression of membrane-associated phospholipase A2 shows malignant potential of human breast cancer cells.

BACKGROUND: Recently, the authors reported that membrane-associated phospholipase A2 (M-PLA2) was one of the acute phase reactants and increased in serum of patients with various malignant tumors. METHODS: M-PLA2 concentrations in tissue specimens from 78 breast cancers, 16 benign breast tumors, and 10 normal breast tissues were determined by a specific radioimmunoassay recently developed. Immunohistochemical staining was performed on all specimens by the avidin-biotin-peroxidase method. RESULTS: Tissue levels of M-PLA2 concentration were significantly higher in breast cancer than in benign breast tumor or normal breast tissue (P < 0.01). Correlation analyses between the tissue concentration of M-PLA2 and clinicopathologic factors showed that tissue M-PLA2 levels were significantly higher in patients with skin or muscle invasion, vessel involvement, and distant metastasis than in those without. In addition, this enzyme concentration was significantly greater in scirrhous carcinoma than in papillotubular or solid-tubular carcinoma. No association was found between M-PLA2 concentration and steroid hormone receptor status. Immunohistochemically, M-PLA2 was preferentially stained in the invading zone of breast cancer tissues, especially in scirrhous carcinoma. Patients with breast cancer with low levels of M-PLA2 showed significantly longer overall survival and disease-free survival compared with those with high levels of this enzyme at the cutoff point of 50 ng/100 mg protein. The combination of estrogen receptor status with M-PLA2 concentration could be a powerful prognostic factor in predicting such survival rates. CONCLUSIONS: M-PLA2 is closely related to the malignant potential of breast cancers, and the M-PLA2 contents in breast cancer tissues could be a new valuable prognostic factor, other than the hormone receptor, in delineating the status of human breast cancer.

Breast↗

PubMed1993

Interleukin 6 stimulates the production of immunoreactive endothelin 1 in human breast cancer cells.

To investigate the potential regulation of endothelin 1 production in human breast cancer cells, we measured the release of immunoreactive endothelin 1 (ir-ET-1) from the MCF-7 and ZR-75-1 breast cancer cell lines in response to various agents including estrogen and tamoxifen as well as several cytokines. ir-ET-1 was detected in conditioned medium of MCF-7 cells and ZR-75-1 cells by specific radioimmunoassay. Among the agents tested, estrogen, tamoxifen, tumor necrosis factor, gamma-interferon, interleukin (IL) 1, and transforming growth factor beta had no effect on ir-ET-1 secretion by these breast cancer cells. However, IL-6 (20 ng/ml) treatment of MCF-7 cells and ZR-75-1 cells caused maximal increases in the amount of ir-ET-1 secreted into the culture medium to 206 and 314% of basal values after 6 h, respectively. This effect of IL-6 on ir-ET-1 secretion was inhibited by actinomycin D and cycloheximide, indicating that IL-6 stimulates de novo synthesis of ir-ET-1 at a transcriptional level. Reverse-phase high performance liquid chromatography coupled with radioimmunoassay in the conditioned medium from IL-6-treated cells revealed one major ir-ET-1 component corresponding to human standard ET-1. The present study demonstrates the potential for IL-6 to stimulate ir-ET-1 production in human breast cancer cells, which may participate in the process of acute phase reactant-like expression of this peptide and/or in the process of IL-6 enhanced breast cancer cell motility, the latter being recently clarified.

Breast Neoplasms↗

PubMed1993

Both CD45RA+ and CD45RA- subpopulations of CD8+ T cells contain cells with high levels of lymphocyte function-associated antigen-1 expression, a phenotype of primed T cells.

Expression of CD45 isoforms and some adhesion molecules on T cells change during T cell activation. In CD4+ T cells, it has been reported that CD45RA is lost and CD45RO is up-regulated when CD4+ T cells are stimulated. This change seemed to be irreversible and thus CD45RA may serve as a marker for virgin T cells and CD45R0 as a marker for memory T cells in CD4+ T cells. In CD8+ T cells, however, the expression of CD45 isoform has been less well understood. We have previously reported the switching of CD45 isoform expression may be reversible and CD8+CD45RA+ T cells may contain preactivated T cells. We present further evidence to support this notion by investigating the expression of lymphocyte function-associated Ag (LFA-1) in relation to CD45 isoform expression in various T cell populations in the human. In the thymus and umbilical cord blood, more than 97% of both CD4+ and CD8+ single positive T cells expressed LFA-1 at a low level. In CD4+ peripheral blood T cells, a high level of LFA-1 expression was found only in the CD45RA- population: 98% of CD45RA+ cells were LFA-1low. In CD8+ peripheral blood T cells, in contrast, a distinct population of LFA-1high cells was found in CD45RA+ subset, comprising about 45% of this subset in a 32-yr-old donor. In 7 days after stimulation with PHA, all CD4+ and CD8+ T cells, irrespective of their CD45 isoform expression, were LFA-1high. The proportion of CD45RA+ cells decreased in CD4+ but slightly increased in CD8+ T cells after the stimulation. These results support the notion that CD45RA and CD45R0 mark virgin and memory T cells respectively in the CD4+ T cells, and that CD8+CD45RA- T cells are primed. However, the validity of CD45RA as a marker of virgin cells in CD8+ T cells is seriously questioned.

Adult↗

PubMed1993

Age-related accumulation of LFA-1high cells in a CD8+CD45RAhigh T cell population.

The differential expression of CD45 isoforms has been suggested as a marker for stages of post-thymic T cell development, that is, CD45RA+CD45R0-T cells and CD45RA-CD45R0+ T cells are supposed to be virgin and memory cells respectively. Recently, several adhesion molecules have been shown to be up-regulated on the cell surface of memory T cells, and have been suggested to serve as a memory marker. In this study, we investigated the levels of LFA-1 expression on T cells in various subpopulations defined by CD45 isoform expression in donors of various ages. In CD4+ T cells, the proportion of LFA-1high cells among CD45RAhighCD45R0- T cells remained low in all age groups and did not show significant accumulation with age. CD4+CD45RA-CD45R0high T cells expressed LFA-1 at a higher level than CD4+CD45RAhighCD45R0- T cells. Thus, the currently prevailing view that CD45RA and CD45R0 can be markers for virgin and primed cells was consistent with LFA-1 expression in CD4+ T cell population. In CD8+ T cells, however, CD45RAhighCD45R0- T cells consisted of two distinct subpopulations, LFA-1low and LFA-1high cells, whereas CD45RA-CD45R0high T cells were almost exclusively LFA-1high. When CD29 expression was examined in place of LFA-1 expression, similar results were obtained; CD45RAhigh CD45R0- T cells consisted of two distinct subpopulations, CD29-to low and CD29high cells, while CD45RA-CD45R0high T cells were mostly CD29high. The proportion of LFA-1high cells in the CD8+CD45RAhigh T cell subpopulation increased significantly as a function of age (r = 0.9, p < 0.001). It ranged from 8% in a 14-year-old donor to 94% in a 79-year-old donor. Furthermore, the proportion of CD8+CD45RAhighLFA-1high cells in the CD8+ T cell population increased significantly as a function of age (r = 0.85, p < 0.001). On the other hand the proportion of LFA-1high cells in CD8+CD45RA- T cell subpopulation exceeded 90% in most donors irrespective of age. These results indicate that the CD8+CD45RAhighCD45R0- T cell subpopulation contains a considerable number of LFA-1high cells and CD29high cells, phenotypically similar to previously activated cells. Thus, in terms of LFA-1 and CD29 expressions, the simple scheme that CD45RA is a marker of virgin cells is not applicable to the CD8+ T cell population.

Adolescent↗

PubMed1993

Plasma tumour necrosis factor-alpha (TNF-alpha) levels in patients with burns.

Levels of plasma tumour necrosis factor-alpha (TNF-alpha) were determined consecutively in 42 patients with burns > 20 per cent of the total body surface area using an enzyme-linked immunosorbent assay. In the early period after injury (including the period of burn shock), 24 patients had detectable TNF-alpha levels in their plasma. However, the plasma TNF-alpha levels at the time of admission were very low and did not correlate with the extent of the burn or the prognosis. In contrast, the maximum plasma TNF-alpha level over the whole clinical course was significantly correlated with the area of the burn and the prognosis. No correlation was found between the plasma TNF-alpha and plasma endotoxin levels. TNF-alpha may be produced locally in infected burns and monitoring of plasma TNF-alpha levels may be a useful prognostic indicator for burns patients.

Adult↗

PubMed1993

Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer.

Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were positive for both receptors were found to contain the highest t-PA activity and antigen. This study provides provocative evidence suggesting a possible differential significance of t-PA and u-PA expression in human breast cancer.

Bone Neoplasms↗

PubMed1993

Breast cancer prognosis is poor when total plasminogen activator activity is low.

Plasminogen activator (PA) is a serine protease which exists in two forms: tissue-type (t-PA) and urokinase-type (u-PA). The total PA activity was measured in tumour extracts of 235 breast cancer patients who were followed for a median of 8.5 years after surgery. Patients were initially divided into three groups with low (< 60 units mg-1 protein), intermediate (60-300 unit mg-1 protein), or high (> 300 unit mg-1 protein) total PA activity in tumour extracts. The PA activity was not significantly associated with the recognised prognostic factors of age, menstrual status, tumour size, lymph node involvement, histologic type, grade of anaplasia, and/or vessel involvement. A significant association was found between total PA activity and the oestrogen receptor (ER) or progesterone receptor (PgR) status. Among receptor-positive tumours, a significantly greater proportion of patients had high PA activity in their tumour extracts. Breast cancer patients with low total PA activity had a significantly shorter disease-free and overall survival rate when compared to those with intermediate or high PA activity. In univariate and multivariate analyses, total PA activity (< 60 unit mg-1 vs > or = 60 unit mg-1 protein) was found to be a significant prognostic factor for disease-free and overall survival of about the same import as lymph node involvement. Furthermore, the combination of total PA activity and nodal status could be even more precise in predicting survival times and probabilities in individual patients. This retrospective study demonstrates the total PA activity is a valuable prognostic factor in determining prognosis in human breast cancer.

Breast Neoplasms↗